IUL Science Internship Program, San Diego, CA, USA.
San Diego Supercomputer Center, University of California San Diego, La Jolla, CA, USA.
J Alzheimers Dis. 2022;86(2):841-859. doi: 10.3233/JAD-215502.
The current standard for Alzheimer's disease (AD) diagnosis is often imprecise, as with memory tests, and invasive or expensive, as with brain scans. However, the dysregulation patterns of miRNA in blood hold potential as useful biomarkers for the non-invasive diagnosis and even treatment of AD.
The goal of this research is to elucidate new miRNA biomarkers and create a machine-learning (ML) model for the diagnosis of AD.
We utilized pathways and target gene networks related to confirmed miRNA biomarkers in AD diagnosis and created multiple models to use for diagnostics based on the significant differences among miRNA expression between blood profiles (serum and plasma).
The best performing serum-based ML model, trained on filtered disease-specific miRNA datasets, was able to identify miRNA biomarkers with 92.0% accuracy and the best performing plasma-based ML model, trained on filtered disease-specific miRNA datasets, was able to identify miRNA biomarkers with 90.9% accuracy. Through analysis of AD implicated miRNA, thousands of descriptors reliant on target gene and pathways were created which can then be used to identify novel biomarkers and strengthen disease diagnosis.
Development of a ML model including miRNA and their genomic and pathway descriptors made it possible to achieve considerable accuracy for the prediction of AD.
目前阿尔茨海默病(AD)的诊断标准通常不够精确,例如记忆测试,或者不够侵入性或昂贵,例如大脑扫描。然而,血液中 miRNA 的失调模式有可能成为 AD 非侵入性诊断甚至治疗的有用生物标志物。
本研究旨在阐明新的 miRNA 生物标志物,并为 AD 的诊断创建机器学习(ML)模型。
我们利用了与 AD 诊断中已确认的 miRNA 生物标志物相关的途径和靶基因网络,并创建了多个模型,以便基于血液图谱(血清和血浆)中 miRNA 表达的显著差异进行诊断。
基于过滤后的疾病特异性 miRNA 数据集训练的最佳血清 ML 模型能够以 92.0%的准确率识别 miRNA 生物标志物,而基于过滤后的疾病特异性 miRNA 数据集训练的最佳血浆 ML 模型能够以 90.9%的准确率识别 miRNA 生物标志物。通过对 AD 相关 miRNA 的分析,创建了数千个依赖于靶基因和途径的描述符,然后可以使用这些描述符来识别新的生物标志物并加强疾病诊断。
开发包括 miRNA 及其基因组和途径描述符的 ML 模型,使得对 AD 的预测能够达到相当高的准确性。